title: In vivo MRI detection of carotid atherosclerotic lesions and kidney inflammation in ApoE-deficient mice by using LOX-1 targeted iron nanoparticles.
abstract: Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) plays a key role in atherosclerotic plaque initiation, formation and rupture, as well as in hyperlipidemia-induced glomerular disease. Here we report a sensitive, specific and biocompatible LOX-1-targeted-USPIO for the noninvasive MR imaging of LOX-1 within carotid atherosclerotic lesions and glomerular disease in apoE-deficient mice. In vitro analysis showed the highest uptake of targeted USPIOs in only activated RAW264.7 macrophages, and in vivo MRI studies showed signal loss in carotid atherosclerotic lesions after administration of targeted USPIOs at 8h and 24h. These areas of signal loss were correlated with the presence of nanoparticles in the atherosclerotic lesions, and immunohistochemistry and Perl's staining confirmed the co-localization of the LOX-1/macrophages/MMP-9 and targeted nanoparticles. Finally, additional studies suggest that this targeted probe may have potential to noninvasively image early glomerular disease. This finding may provide important methods for characterizing vulnerable atherosclerotic plaques and hyperlipidemia-induced glomerular diseases.
  
  
  BACKGROUND
  A functionalized USPIO-based negative contrast material was used in this study, demonstrating feasibility of sensitive MRI-based detection of atherosclerotic plaque formation in the carotid arteries and in the renal cortex, paving the way to potential future clinical applications.
authors.affiliation: Jiangsu Key lab of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wen
authors.affiliation: Jiangsu Key lab of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Liu
authors.affiliation: Jiangsu Key lab of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Biomedical Engineering, Emory University/Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Steven Scott
authors.initials: SS
authors.lastname: Harris
authors.affiliation: Jiangsu Key lab of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Yu-chen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Radiology, Wells Fargo Faculty Scholar, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: King C
authors.initials: KC
authors.lastname: Li
authors.affiliation: Jiangsu Key lab of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Sheng-hong
authors.initials: SH
authors.lastname: Ju
authors.affiliation: Jiangsu Key lab of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China. Electronic address: gjteng@vip.sina.com.
authors.forename: Gao-Jun
authors.initials: GJ
authors.lastname: Teng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media; D003911:Dextrans; D017353:Gene Deletion; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000235:genetics / Q000473:pathology*; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000473:pathology*; D051127:Scavenger Receptors, Class E / Q000032:analysis*
chemical_list: D001057:Apolipoproteins E; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; C097921:ferumoxtran-10
keywords: Atherosclerosis; LOX-1; Magnetic resonance imaging; USPIO